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It is still not clear how global warming will affect the global carbon cycle, either in terms of the magnitude of the effect or even its sign. Help in answering that question will come from long-term field-based experiments designed to explore carbon cycle-climate feedbacks in an ecosystem context. Melillo et al. performed a 26-year soil-warming experiment in a mid-latitude hardwood forest (see the Perspective by Metcalfe). Warming has resulted in a complex pattern of net carbon loss from the soil. These results support projections of a long-term, positive carbon feedback from similar ecosystems as the world warms.Science, this issue p. 101; See also p. 41In a 26-year soil warming experiment in a mid-latitude hardwood forest, we documented changes in soil carbon cycling to investigate the potential consequences for the climate system. We found that soil warming results in a four-phase pattern of soil organic matter decay and carbon dioxide fluxes to the atmosphere, with phases of substantial soil carbon loss alternating with phases of no detectable loss. Several factors combine to affect the timing, magnitude, and thermal acclimation of soil carbon loss. These include depletion of microbially accessible carbon pools, reductions in microbial biomass, a shift in microbial carbon use efficiency, and changes in microbial community composition. Our results support projections of a long-term, self-reinforcing carbon feedback from mid-latitude forests to the climate system as the world warms.